College of Medicine and Health - Masters by Research Theses

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Assessment of respiratory motor units in the mdx mouse model of Duchenne muscular dystrophy
(University College Cork, 2021-03-22) Murphy, Kevin H.; O'Halloran, Ken D.; Burns, David
Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease characterised by the absence of the structural protein dystrophin. Respiratory failure is the leading cause of premature death in DMD. Although respiratory insufficiency is recognized as a hallmark of DMD, respiratory control is relatively understudied. We hypothesized that enhanced drive in respiratory motor pathways preserves ventilatory capacity compensating for severe respiratory muscle weakness. Male wild-type (n=23) and mdx (n=23) mice were studied. Breathing was examined during normoxia and chemo-challenge with hypercapnic-hypoxia. In urethane (1.7 g/kg i.p.) anaesthetised mice, diaphragm, external intercostal and genioglossus electromyogram (EMG) and motor unit recordings were performed during baseline conditions and in response to chemo-stimulation. Diaphragm muscle function was examined ex vivo. Diaphragm muscle function is severely impaired in young mdx mice. Despite substantial diaphragm muscle weakness, freely-behaving mdx mice can increase ventilation during chemostimulation with hypercapnic-hypoxia. Motor unit recordings revealed an increase in the number of active units for diaphragm and genioglossus muscle. There were no major differences in the firing frequency of motor units in the respiratory muscles. Diaphragm EMG activity was depressed in mdx mice during baseline and maximum chemostimulation, compared to wild-type. In conclusion, severe mechanical disadvantage of the diaphragm is evident across a range of stimulation frequencies, yet there is a preserved capacity to raise ventilation in young mdx mice indicating a significant ventilatory reserve. Motor unit remodelling is evident in the diaphragm of mdx mice, but ultimately diaphragm EMG activity is impaired. The combination of reduced neural activation of the diaphragm and intrinsic weakness reveals major compromise in the neuromuscular function of the diaphragm in mdx mice as early as 8 weeks of age. The novel observations of this study coupled with other work by our group suggest that support from accessory muscles is critical to the support of respiratory performance in mdx mice, which may have relevance to DMD.
Assessment of the potential environmental impacts arising from mercury-free dental restorative materials
(University College Cork, 2019-12) Binner, Hannah; Sullivan, Timothy; Harding, Mairead; Environmental Protection Agency
The field of dentistry and with it, the application of dental filling materials, is currently undergoing changes to adopt sustainability and environmental considerations into the clinical environment. This was largely triggered by the reduction of all products in use that contain Hg (mercury), including dental amalgam, through the Minamata Convention of 2013, which has in turn caused a rise in Hg-free dental filling materials that are now becoming increasingly nano-filled. The focus of this study is on the particles released from Hg-free dental fillings. Knowledge gaps regarding the particle load and potential ecotoxicity of the particulate matter resulting from Hg-free materials exist. Moreover, the widely known environmental and human health impacts of Hg contained in dental amalgam have led to the widespread introduction of an amalgam capture device, the amalgam separator. Amalgam separators capture Hg and dental amalgam particles before wastewater discharge occurs. These amalgam separators are required to be installed in Ireland since the 1st of January 2019 in accordance with EU Directive 2017/852. The overarching objective of this thesis has been to assess whether existing amalgam separators are also effective in capturing particulate matter resulting from the use of Hg-free dental filling materials. In order to meet this objective, this study has assessed the wastewater and amalgam separator capture efficiency in three dental practices in Cork, Ireland. Three dental practices were selected based on the type of amalgam separator in use and focus of service based on private or public practice and high, medium or low utilisation. Physical and chemical parameters of dental wastewater (DWW), including pH, temperature, conductivity, Total suspended solids (TSS) and Total Dissolved Solids (TDS) have been measured. Detailed analysis of particles found in these wastewater streams has been conducted using optical and scanning electron microscopy. The potential ecotoxicity of these waste streams has also undergone preliminary assessment by conducting standardised Daphnia magna immobilisation tests. The results indicate that variation in the discharged DWWs exists, which is likely linked to the use of disinfection products, and has led to extreme observations of pH, conductivity, Total suspended solids and Total dissolved solids. Ecotoxicity results confirmed this and showed that the raw DWW caused an EC50 response at concentrations between 0.1 to 6.69 % DWW/L medium. The particulate load in the three DPs was substantial. A high abundance of microparticles was identified and trends were consistent across the three DPs. It was therefore concluded that amalgam separators may not be sufficient in capturing the particulate matter released from Hg-free dental filling materials. Further research is needed to identify the environmental fate of the particles that are released, particularly nanomaterials, as they have the potential to remain in the water after wastewater treatment has occurred.
Bowel symptom management following sphincter-sparing surgery for rectal cancer
(University College Cork, 2019-10-07) O'Sullivan, Mairéad; Landers, Margaret; Hegarty, Josephine
Aims: The aim of this study is to determine the content, format and mode of delivery of an intervention for patients following sphincter-sparing surgery who have experienced altered bowel function. Background: The treatment of rectal cancer often causes the development of life-altering bowel symptoms. Healthcare professionals play a pivotal role in supporting patients in their management of symptoms but increasingly it is recognised that care often becomes the patients’ sole responsibility. Numerous studies have identified the need to support patients in the self-care of their bowel symptoms and to develop interventions to facilitate same. Yet there is a dearth of literature around interventions to support patients with the symptoms specific to rectal cancer treatment, to self-care for their bowel symptoms, which do not involve the use of invasive techniques or continuous health-care professional input. Design: A qualitative descriptive design. Methods: To determine the content, format and mode of delivery of an intervention a purposeful sample of five patients and ten healthcare professionals were interviewed through individual semi-structured, audio-recorded interviews. Participants included those who had undergone sphincter-sparing surgery for rectal cancer and those involved in their care. An initial pilot study was carried out prior to conducting the main study. Data were analysed utilising deductive content analysis and data coded according to pre-determined categories. The research was underpinned by the Symptom Management Theory and also utilised the Medical Research Council Framework Guidance for the Development of Complex Interventions. Findings: Participants acknowledged the existence and impact of bowel dysfunction following surgery for rectal cancer, often continuing for a number of years post-treatment and varying from frequency, urgency and tenesmus to skin irritation and pain, in addition data analysis revealed multiple symptoms which occurred and in addition the variability of these symptoms in relation to severity, duration and associated degree of bother. The psychological and social impact of symptoms was also evident. All participants (n=15) acknowledged issues within the current practice around educating patients about the incidence, treatment and self-care of bowel symptoms, often resulting in prolonged periods of symptom experience or use of unhelpful or unsafe self-care strategies. Additionally, participants identified the need for the development of an intervention to support patients. Patients and healthcare professionals identified a phone application as a convenient and accessible method but also acknowledged the need for a booklet/written mode to cater for those less able to utilise technological formats. Of interest some healthcare professionals felt that a leaflet format would be preferable as a means of intervention delivery, this contrasted with the views of patients who felt an online or phone application format would allow greater accessibility and convenience. The intervention proposed is a multi-modal format which provided patients with information around medication, diet, skin care, resources, alternative therapies and pelvic floor exercises. Finally, throughout all interviews the need for a human contact, i.e. ability to access a healthcare professional, was highlighted as a pivotal and important feature of any intervention. Conclusion: This research has provided insights into the bowel symptoms experienced by patients following sphincter-sparing surgery for rectal cancer, the impact of these symptoms, the strategies utilised to manage these symptoms. Importantly, this study identified the need to create an intervention to allow patients to manage their symptoms in a safe and evidence-based manner and determined the appropriate content, format and mode of delivery using the findings of interviews with both affected patients and those involved in their care.
Caregiver readiness for hospital discharge of an older adult
(University College Cork, 2020-04-30) Galvin, Eileen; Wills, Teresa; O'Mahony, Mairin; University College Cork
Aim: To explore caregiver readiness for the hospital discharge of an older adult. Background: Older adults rely on their caregivers during hospital discharge. However, caregivers are not routinely included in discharge preparation. Caregivers’ experiences of hospital discharge have been studied retrospectively between one week and three months. However, no study used the attributes of readiness to guide the research and none of the caregivers were interviewed within twenty-four hours of hospital discharge when experiences are foremost in their minds. Method: The study was qualitative descriptive. Using the attributes of readiness for hospital discharge to develop an interview guide, nine semi-structured interviews with caregivers took place within 24 hours of hospital discharge during the summer of 2017. Data were analysed using content analysis. Findings: The findings that emerged from the data are presented under the four attributes of readiness for hospital discharge: Caregivers’ physical readiness, Caregivers’ psychological readiness, Support for caregivers and Information and knowledge. An overarching category of “Wanting to do what’s best” also emerged. Findings highlight that overall, caregivers are not ready to take the older adult home from hospital. In addition, low referral rates of older adults to PHN services were highlighted. Conclusion: The results of this unique study provide a picture of the current state of caregiver readiness for the hospital discharge of an older adult. In addition, the need for early preparation of caregivers for the hospital discharge of an older adult is highlighted which includes early referral to PHN services. Impact: Nursing staff require focused education on the preparation of caregivers for hospital discharge. In addition, development of a tool to assess caregiver physical and psychological readiness is necessary. Further research and assessment of caregivers longitudinally will give more insight into caregiver needs, experience and progress. Ultimately, ensuring caregivers are ready for hospital discharge of an older adult will assist older adults remaining at home, which is ultimately where they want to be.
Children’s voices: participation in decision-making within the goal setting process in occupational therapy
(University College Cork, 2019-12-17) O'Connor, Deirdre; Lynch, Helen; Boyle, Bryan
Introduction: Children’s participation in decision-making remains an under-researched area, especially in the context of Occupational Therapy. Therefore, the principal aim of this research was to explore the experience of children in relation to having their voices heard within goal-setting in Occupational Therapy. This is consistent with Article 12 of the United Nations Convention on the Rights of the Child, 1989) and with Occupational Therapy’s commitments to client-centred practice (World Federation of Occupational Therapy, 2019). Study Design: Informed by the approaches of ethnography, this qualitative study had 17 participants including 6 children, 5 parent(s)/guardian(s) and 6 occupational therapists to gain multiple perspectives from those involved in goal-setting. Semi-structured interviews were conducted with all participants, while a mosaic approach offered children multiple methods to communicate their experience. Findings were analysed using a thematic analysis approach. Findings: On analysis, 3 themes emerged: 1) Where goal setting exists: Experiences of paediatric Occupational Therapy services in an Irish context; 2) Children’s right to be heard: Knowledge, views, attitudes and power and 3) Goal setting processes … power and influence. Findings suggest that Occupational Therapy goals are, for the most part, adult directed and as such children’s voices are subsumed by adult agendas, priorities, and adult-led services. Conclusion: Findings illustrate that despite healthcare professionals valuing the voice of children, children and their parent(s)/guardian(s) are not consistently included in goal-setting. Numerous factors impacting children’s participation in decision-making were found such as awareness and attitudes towards children and their rights as well as the age and ability of children, for example. Few formal guidelines or standards exist as to how to operationalise a child’s right-based approach in practice.
Deciphering the role of microbially-derived metabolites on the microbiota-gut-brain axis
(University College Cork, 2021-01-25) Spichak, Simon; Cryan, John; Dinan, Timothy G.; Science Foundation Ireland; Irish Research Council
The trillions of microbial organisms residing in the gut, microbiota, are now recognized as major modulators of physiology and health, quickly becoming one of the most exciting emerging areas in neuroscience. Preclinical and clinical research alike suggests that the metabolites produced by these gut microbes modulate brain, behavior and disease. Short-chain fatty acids, tryptophan metabolites and bile acids are promising targets for new microbiome-based therapies. But, little is known about their mechanisms. To this end, the second chapter of the thesis collates 278 studies relating to the human microbiota-gut-brain axis, identifying trends and technical/bioinformatics limitations. These studies across different disorders of the brain as well as healthy human behavioral functions. Then a 35 of these studies was reanalyzed with an up-to-date bioinformatics pipeline. New tools, mainly the gut-brain modules provide a predictive framework for identifying whether these gut microbial metabolic pathways are dysregulated in brain diseases and disorders. We uncovered evidence of disease-related alterations in microbial metabolic pathways in Alzheimer’s Disease, schizophrenia, anxiety and depression. Previous human studies suggest that astrocyte immunity and metabolism is affected by short-chain fatty acids. Thus we grew primary male and female mouse astrocyte cultures, treating them with acetate, butyrate and propionate. Butyrate treatment (0 – 25μM) increased gene expression of Bdnf and Pgc1-α expression, implicating histone-deacetylase inhibitor pathways only in female cells. Acetate (0 – 1500 μM) positively correlated with Ahr and Gfap expression in males, suggesting an immune modulatory role. These findings show a novel sex-dependent impact of acetate and butyrate, but not propionate on astrocyte gene expression. These studies increase understanding of microbial metabolites and how they might impact the brain. It also provides guidance to improve and direct future investigations aimed at identifying the mechanisms of other metabolites.
Defining the patient safety trajectory of breast cancer at a National Cancer Centre
(University College Cork, 2023) Forrest, Clara; Ó Tuathaigh, Colm; Health Service Executive; University College Cork
Introduction: One in seven Irish women will develop breast cancer in their lifetime. A well-researched management pathway commences thereafter, involving multiple treatment modalities and specialities. In contrast, there is sparse research examining the patient safety trajectory that mirrors this clinical journey. Learnings from previous events can illuminate this otherwise unknown patient safety trajectory of those with breast cancer. Furthermore, there is little known of patients’ and doctors’ views and experiences of this patient safety trajectory. Aims: This study aimed to characterise patient safety incidents that have occurred during breast cancer care, their contributory and preventative factors, outcome and impact. Using this data, patient safety trajectories were created. In addition, this paper aimed to explore the patient safety views and concerns of patients receiving and doctors providing breast cancer care. Methods: Anonymous, quantitative patient and doctor questionnaires were used. In addition, data related to medical negligence claims involving breast cancer and handled by the State Claims Agency was analysed. Pearson chi-squared test and Fisher’s exact test were utilised for categorical data. The median degrees of harm were used to construct trajectories. Results: 83 patient safety incidents were included (61 medical errors and 22 medical negligence claims). Failure or delay to correctly diagnose was the most commonly implicated adverse event type overall (n=32/83, 38.6%) and was involved in a higher proportion of medical negligence claims than medical errors (p=0.01). Forty percent of events occurred in the outpatient department (n=33/83) and 31% of events took place before a patient’s formal breast cancer diagnosis (n=26/83). Inadequate communication was the most common contributory factor. Events during neoadjuvant chemotherapy and after discharge from follow-up had the highest median degree of harm of 4 (Q1-Q3:3.5-4.5 and Q1-Q3:4.0-4.5). More doctors felt patient safety has worsened in the past five years compared to patients (41.4% vs 13.0%) (p<0.001). Twice as many doctors reported that there were inadequate measures in place to prevent medical error compared to patients (54.3% vs 27.2%) (p<0.001). Conclusion: Patient safety incidents during breast cancer care occur in a variety of settings and during all clinical stages but often occur before diagnosis and involve inadequate communication. Doctors who provide breast cancer care have a more pessimistic outlook on patient safety compared to patients and are more concerned about medical error in breast cancer care. Addressing and acting on the experiences and concerns of those involved in breast cancer care is vital to improve patient safety trajectories for breast cancer patients.
Designing public playgrounds for inclusion: Universal Design for Play (UDP), a tailored perspective
(University College Cork, 2022-08-31) Moore, Alice; Lynch, Helen; Boyle, Bryan; Irish Research Council
To extend knowledge on how to enable outdoor play, social participation, and inclusion in public playgrounds, the overall aim of this thesis is to establish an evidence base for using Universal Design (UD) for public playground design. The scope of this doctoral research encompassed a multi-layered approach to understanding this complex concept of UD from a higher conceptual level as well as an applied level. It includes five studies that employed multiple methods to review published and grey literature as well as explore the perspectives of “professional experts” and “user experts”. Study I included a review of evidence for using UD in public playground design. Specifically, a scoping review of peer reviewed literature was undertaken to identify and synthesise what is known from published, peer reviewed studies about inclusive public playgrounds, underpinned by a commitment to understanding the concept of UD as it applies specifically to public playground design. Findings show that although UD is recognised to have the potential to support the design of public playgrounds, the evidence is currently very sparse and identified the gap in knowledge internationally of how UD is understood as a concept. Study II included a review of the conceptual understanding of UD in public playground design. Indeed, this consisted of a scoping review to determine how UD and related non-discriminatory planning and design concepts are represented in the context of published research exploring public playground design for inclusion. Findings revealed that that the terms UD, inclusive design, accessibility, and usability are all being used to describe non-discriminatory planning and design processes arbitrarily and without regard for higher or lower order concepts, which has potentially led to inconsistency and confusion. Altogether, diverse interpretations of UD were evident; for some UD was understood as a basic concept resulting in accessibility, for others, UD was more holistic in terms of designing for inclusion. In Study III, scoping review search methods were developed and applied to synthesise findings from a review of international grey literature guidelines for the design of public playgrounds for inclusion and sought to determine the evidence for using UD and play value in public playground design. Findings highlighted that although UD is recognised to have the potential to support the design of public playgrounds, inconsistent design approaches, principles, and recommendations, were communicated among the included guideline documents. However, the core concept of inclusion underpinned all guideline documents, and a tailored application of UD dominated. Study IV involved survey methods to determine the ways in which UD is understood and implemented, when planning, designing, and/or providing public playgrounds, from the perspectives of a national sample of playground professionals in the Republic of Ireland. The findings show that playground professionals recognise the importance of UD and implement UD in various ways. However, significant barriers to implementing UD included a lack of knowledge and good practice guides for embedding UD. To counteract these barriers, a variety of opportunities, initiatives and training prospects were identified. In Study V, a qualitative descriptive study sought to explore the experiences of using playgrounds, as well as the reasons for non-use, from child and adult perspectives, through the lens of play and play value to inform UD. Findings emphasised that although children and adults value playgrounds as spaces for outdoor play, social participation, and inclusion, playgrounds are not always useable, and do not always meet the needs of families. Participants in this study confirmed that there are variable standards when it comes to playground provision, and some facilities lack essential elements for outdoor play, social participation, and inclusion. Nevertheless, participants offered many creative ideas to improve the usability of playgrounds, and therefore, identified potentially practical ways of implementing UD in playground design for inclusion (Chapter Seven). In conclusion, this doctoral research contributes with an evidence base for using UD for public playground design both at a conceptual and an applied level. It challenges the current UD concept and argues for further conceptual refinement to consolidate the importance and future application of UD for Play (UDP) in the design of public playgrounds that promote outdoor play, social participation, and inclusion. Moving forward the challenge is to promote the universal establishment of inclusive public playgrounds that offer high play value and include all persons in everyday occupations without injustice.
Determining the biopsychosocial factors of chronic pain in older adults to inform the development of a risk appraisal checklist for use in long term care: a Delphi study
(University College Cork, 2021) Clifford, Michelle; Cornally, Nicola; Fitzgerald, Serena
Background: In long term care (LTC), the prevalence of pain is 43% (van Kooten et al., 2017), and this, coupled with the high prevalence of dementia (Zimmerman et al., 2014), lends itself to complex practice issues in terms of pain assessment. The American Society of Pain Management Nursing published the hierarchy of pain assessment techniques developed by Pasero and McCaffery (2011) to guide pain assessment in people unable to self-report. The first step of this framework focuses on awareness of potential causes of pain, hence the importance of identifying the biopsychosocial factors associated with chronic pain in older adults. Improving pain assessment can improve older adults' quality of care and the ultimate quality of life. However, very little research has supported the early identification of older persons at risk of unreported chronic pain due to communication impairment or a neurodegenerative disease such as dementia. Using a multi-dimensional lens, this research aims to identify the biopsychosocial factors of chronic pain in older adults to inform the development of a risk appraisal checklist for use in long-term care. Methods: Chen et al. (2016) proposed a four-phase process when employing a Delphi technique to develop a quality instrument. These phases include identifying an expert panel, generating initial factors, and identifying the final factors and instrument development. The first three phases were the focus of this study. Following the identification of an expert panel in chronic pain, phase two involved completing a scoping review to create a list of the initial factors. There was a total of fifty-nine biopsychosocial factors identified from the empirical literature. These factors were used to inform round one of the modified e-Delphi surveys. A consensus agreement rate of 50% was applied for this study for round one, median ≥4 for round 2 and ≥90% agreement for inclusion in round three. Thematic analysis of open-ended responses also took place. Results: Thirteen experts in gerontology and chronic pain participated in a minimum of two rounds. There was a desirable international spread from eight countries, and 68.4% of the experts had >21 years of experience in their field of expertise. The 59 initial factors identified from the scoping review were presented to the experts in round one. Fifty (84.7%) biopsychosocial factors achieved a 50% or greater agreement of factor importance. Sixty-three factors were presented to the expert panel in round two, 33 factors were rerated from round one, nine factors were modified, and the experts identified 21 new factors. The results from round two, a total of fifty-one factors, achieved a median of ≥4 and were presented in round three. The final twenty-two factors that achieved ≥90% consensus agreement in round three for inclusion included; age, female gender, arthritis, lower back pain, malignancy, family history of chronic pain, multiple comorbidities, trauma and/or accident, multiple sites, anxiety and depression, social isolation/loneliness, post-traumatic stress, childhood physical/sexual abuse, maladaptive beliefs, poor sleep hygiene and/or insomnia, substance abuse, low socioeconomic background, chemotherapy medication, history of opioid use and poor access to health care. Conclusion: This study has laid the foundations for future research and innovation in comprehensive pain assessment in older adults, focusing on identifying risk factors in older persons for whom accurate self-report of chronic pain is challenging due to communication and/or cognitive impairment. The twenty-two factors identified from this study will inform the development and testing of the Chronic Pain Risk Appraisal Checklist (C-PRAC) for LTC use.
The development of a core school-based Lámh vocabulary to facilitate effective communication between children with Down syndrome and their communication partners in the first year of mainstream primary school
(University College Cork, 2021-01-08) Lyons, Caoimhe; Frizelle, Pauline; Irish Research Council
Background: In Ireland, the entry-level key word sign (KWS) training for teachers and school staff is the Lámh Module 1 training course, which does not contain vocabulary specifically chosen to support school-age Lámh users. However, if KWS is to be used successfully by children with Down syndrome (DS) in a mainstream school environment, it is essential that communication partners have access to a meaningful, contextually appropriate sign vocabulary. Aim: To identify the Lámh vocabulary needs of children with DS and their communication partners over the course of the first year of mainstream primary school, with the aim of developing a core school-based Lámh vocabulary. Method: Five key groups contributed signs to the core vocabulary: participants with DS in junior infants (n=6), their teachers (n=5), special needs assistants (n=8), and peers (n=9), and the researcher (a Speech and Language Therapist). The researcher contributed signs based on observations of the classroom, the participants with DS contributed signs during guided tours of the school environment, and the teachers, SNAs and peers contributed signs by means of structured interviews. This data collection took place at four time points over the school year. Signs were considered to be part of the core vocabulary if they were contributed five times or more over the course of the year, and by three or more of the groups. Results: The core school-based Lámh vocabulary contained 140 words, including 132 Lámh signs and eight words that do not currently have a Lámh sign. Only 55 (39%) of the 140 signs recommended as core vocabulary for schools are part of the training currently most commonly accessed by school staff. The remaining 77 signs (55%) are part of more advanced training. Conclusion: The current study provides new insights into the complex process of vocabulary selection for children who use Lámh in a mainstream school environment. In addition, it highlights the importance of access to a functional sign vocabulary in facilitating an inclusive approach to education, and enhanced communicative practice by all of those engaging with children with DS in mainstream primary school.
The development of a dementia communication intervention for undergraduate nurses based on the VERA framework
(University College Cork, 2020-08-17) Sisk, Ali-Rose; Naughton , Corina; University College Cork
Background: Patients with dementia experience emotional distress due to difficulties communicating physical and social needs. This is compounded by inadequate dementia communication skills among qualified nurses and student nurses. Aim: The project aims were to adapt a dementia communication training intervention, examine acceptability among undergraduate nursing students and test the feasibility of designing a randomized controlled trial (RCT) to evaluate the intervention. Methods: The intervention involved a 1.5-hour dementia communication workshop based on the VERA framework and used information giving, role play, discussion and student manual. Study Design: A quasi-experimental pre-post control trial was used with mixed-methods data collection (student survey, semi-structured interview and non-participatory observations of students in clinical practice). Results: In total, 49 students completed the post intervention survey (i=26, c=23). There was a significant increase in awareness of person-centred response scores in the intervention group 13.1 (SD1.95), compared to the control group 10.6 (SD3.0), p=0.03, there was no other significant differences. Eleven students were observed interacting with patients with dementia (n=219 interactions). There was no significant difference between the groups with missed opportunity for positive interactions observed in both groups. Qualitative interviews with students (n=8) that received the intervention indicated they valued the training but inconsistently used the dementia communication skills in practice. Barriers to implementing the new skills were a lack of role modelling from qualified staff, busy environment and little emphasis on person-centred interactions in clinical practice. Conclusion: The VERA dementia communication intervention was well received by students and may increase their ability to identify person-centred responses, but this may not change communication behaviour. This feasibility study, suggest that a RCT may not be possible and other pragmatic trail designs should be used to evaluate this education intervention.
An effectiveness study of a parent-child interaction therapy with children with Down syndrome
(University College Cork, 2020-04) Cronin, Sarah Marie; Frizelle, Pauline; O'Toole, Ciara; Down Syndrome Ireland
Background: Parents of children with Down syndrome (DS) often demonstrate directive parenting styles which can impede on their child’s communication development. For that reason, parent-child interaction therapies have shown to be an effective form of early intervention for children with DS as it facilitates parent coaching while also addressing the specific communication needs of children with DS. This study aimed to explore the effectiveness of the PELD (Promotion of Early Language Development) intervention offered by a speech and language therapy (SLT) service for individuals with DS. The study aimed to explore the impact this programme had on the language development and communicative interactions of children with DS, while also exploring the change in the interaction and communication strategies employed by their parents. Methodology: A single-subject multiple-baseline design was employed to evaluate the effectiveness of the PELD intervention. Seven child participants and their mothers took part in the study. All participants were aged between 10-17 months at the time of entry. Three terms of the intervention were offered over a 10 month period and families had the option of completing all or some of the terms. Data was collected over three to five time points depending on when the child commenced the intervention. Standardised assessments, parental report and observational measures were used to capture change for both the parent and child. Results: Improvements in receptive vocabulary, use of key word signs, gesture use and a child’s ability to respond to joint attention were noted in the majority of child participants. Children who attended all three terms of the intervention seemed to benefit the most from the PELD programme as they demonstrated a wide range of gestures, understood the most words and used the most Lámh signs post-intervention as reported by their parents. With regards to parent outcomes, all parents were successful in adapting their parenting style and a notable increase in each parents’ ability to follow their child’s lead, join in and play and incorporate a time delay into parent-child interactions was observed. Parents also used language that was developmentally appropriate for their children and increased their use of labelling and repetition of key words post-intervention. Conclusions: The PELD programme is the first parent-child interaction therapy to be tailored specifically to children with DS who are of a very young age. There was some indication that the PELD intervention can support the development of early language skills and the communicative intentions of young children with DS while also upskilling their parents in specific communication and interaction strategies that promote the language development of their child.
The effects of stressors during early life on hippocampal neurogenesis and microglial activation in the male and female brain
(University College Cork, 2021-04-05) McGovern, Andrew Joseph; Nolan, Yvonne M.; O'Leary, Olivia
Stress during critical periods of brain development and maturation such as adolescence is associated with an increased risk of developing stress-related psychiatric disorders which are more common in women than men. Early life stress such as maternal separation (MS), juvenile stress (JS) and inflammatory insults like lipopolysaccharide (LPS), have been found to induce anxiety and depressive-like behaviours and decrease adult hippocampal neurogenesis in rodents. However, the effects of early life stress on adult hippocampal neurogenesis and associated function have been mostly assessed in male rodents. The impact of early life stress on microglia, which are involved in the regulation of adult hippocampal neurogenesis and dendritic remodelling, has also been predominantly examined in male rodents. Thus, in this study we assessed adult hippocampal neurogenesis and hippocampal microglia following LPS administration in MS juvenile female Sprague-Dawley rats and following JS in male and female Sprague-Dawley rats in adulthood. MS increased the number of newly born hippocampal neurons in the ventral hippocampus, reduced the dendritic complexity of newly born neurons in the whole hippocampus and increased the soma size of microglia, indicating activation. LPS reduced newly born hippocampal dendritic complexity and increased the number of microglia in the dorsal hippocampus. Conversely, LPS administration in MS rats reduced the number of microglia in the dorsal hippocampus and MS attenuated microglial activation in response to LPS. LPS administration in MS increased dendritic complexity in the granule cell layer (GCL) and further reduced dendritic complexity in the ventral but not dorsal hippocampus of juvenile female rats. JS did not affect hippocampal neurogenesis in adult male or female rats but reduced the cell soma size of microglia in the GCL in the dorsal hippocampus of females. We observed significant sex differences in adult rats; females had fewer newly born neurons with less dendritic complexity in the dorsal hippocampus than males. There were also fewer microglia in the molecular layer (ML) of the hippocampus in adult female than male rats. Together the data here shows that the effect of early life stressors differentially affects hippocampal neurogenesis and hippocampal microglia dependent on age, sex and subregion of the hippocampus analysed.
Epitope mapping of the E2 glycoprotein, including the hypervariable region 1, of the hepatitis C virus genotype 3a, in the context of humoral immune pressure
(University College Cork, 2020-12) Walsh, Nicole Ellen; Fanning, Liam J.; O'Farrelly, Cliona; Bristol-Myers Squibb
The hepatitis C virus (HCV) is an enveloped +ssRNA virus, belonging to the family Flaviviridae. HCV is notable for displaying extraordinary genetic diversity and variability, having seven recognised genotypes and over sixty subtypes. HCV is responsible for the disease known as hepatitis C, which is associated with cirrhosis and hepatocellular carcinoma (HCC). The Global Hepatitis Report released by the World Health Organisation (WHO) in 2017 estimated that viral hepatitis was responsible for 1,340,000 deaths in 2015. The report also estimated that 71,000,000 people have ongoing HCV infections. HCV is largely transmitted via exposure to infected blood, with intravenous drug use accounting for approximately 55% of cases. HCV infections can be categorised as acute or chronic. During chronic HCV infections, antibodies (Abs) are produced against HCV - however, the host Abs are unable to neutralise HCV and only accelerate the evolution of circulating HCV variants. HCV variants resistant to the current generation of host Abs become the dominant variant through selective pressure. The variants of HCV within a host are known as quasispecies. Although the host Ab response is not able to resolve the chronic HCV infection, some Abs can bind to particular HCV variants. These Abs form complexes with virus particles and are known as AAVs (antibody-associated virus). AAVs are detectable in the blood of patients with chronic HCV infections and examination of these AAVs could reveal conserved viral structures and vulnerable HCV epitopes. Twenty genotype 3a serum and plasma samples from patients with chronic HCV infections were obtained from the National Virus Registry Laboratory (NVRL) and from the Molecular Virology Research and Diagnostic Laboratory (MVDRL). HCV genotype 3a was chosen for this research project given its prevalence (estimated to account for 17.9% of chronic HCV infections), resistance to treatment, and increased risk of causing severe steatosis and HCC when compared to other genotypes. Building on previous research carried out by the MVDRL, the patient samples were screened for the presence of AAVs. Initially, AAV+ samples were going to be processed and used to generate HCV pseudoparticles (HCVpp). The HCVpp system is a model system that incorporates the E1E2 glycoprotein from HCV into a plasmid. The E1E2 glycoprotein is responsible for HCV entry and infection, meaning the HCVpp can be used to infectivity and Ab neutralisation assays. However, the E1E2 glycoproteins could not be extracted from the AAV+ patient samples. Instead, the IgG from the AAV+ samples was extracted and used for a series of neutralisation experiments on HCV pseudoparticles generated using the HCV H77 isolate. H77 (GenBank: AAB67037.1) is an infectious genotype 1a isolate that has undergone complete genome sequencing. The Abs that showed the greatest neutralisation potential against the H77 pseudoparticles were selected for epitope mapping. The epitope mapping procedure tested the selected Ab samples against a synthesised H77 E2 glycoprotein structure, and characterised the sites where the patient Abs bound to the synthesised E2. This revealed vulnerable epitopes on the HCV E2 glycoprotein. The epitope mapping also revealed a large number of glycosylation sites around the vulnerable epitopes – a phenomenon known as glycan shielding. Glycan shielding is used by a number of viruses (including HCV and HIV) to protect conserved and vulnerable epitopes from Abs. However, strategies are being developed to counter viral glycosylation, including modifications to glycosylation sites and the use of polysaccharides derived from non-mammalian sources as therapeutic agents against glycosylated viruses.
The evaluation of estradiol and indomethacin for incorporation into microneedle formulations
(University College Cork, 2022) Lalchandani, Akash Parsram; Crean, Abina; Faisal, Waleed; Enterprise Ireland
The objective of this thesis is the technical evaluation of the suitability of drug substances, estradiol and indomethacin, for incorporation into a patented dissolvable microneedle (DMN) platform technology for intradermal drug delivery. Estradiol and indomethacin were chosen based on their physicochemical properties (melting point, glass transition temperature, amorphous solid state after melt-cooling) which were favourable for manufacturing microneedles using the melt DMN technology. Oral dosage forms of both drugs, and transdermal patches of estradiol are available in the market. Currently no indomethacin transdermal patch formulation is available. This project aims to assess the feasibility of developing dosage forms of both drugs for microneedle-assisted, intradermal delivery. The research presented, initially provides a background to the drivers and challenges related to the development of microneedle (MN) drug combination products for inclusion in the mainstream pharmaceutical and medical device market. The thesis then focuses on the experimental studies evaluating the feasibility of developing DMN from the drug substances of interest, estradiol and indomethacin. Melt-cooled samples of both drugs were also prepared to simulate the processing stress of the DMN manufacturing process. Melt-cooled samples were evaluated for solid-state form by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD), and chemical composition by high performance liquid chromatography. Microneedle formulations of both drugs were produced using a previously developed manufacturing process and their mechanical strength and ability to penetrate pig skin analysed. A stability study was conducted to evaluate chemical and solid-state stability of the melt-cooled samples at 3 storage conditions: condition A (25°C/60% RH), condition B (40°C/ 75% RH), and condition C (2°C to 8°C in nitrogen filled vials) over a 3 month time period. The melt-cooled solid form of both drugs post melting was found to be chemically stable over the period of 3 months when stored at all 3 storage conditions studied. The amorphous melt-cooled samples of both drugs showed greatest stability at 2°C to 8°C in nitrogen. However, DSC and PXRD results identified crystallisation of the melt-cooled estradiol and indomethacin samples to when stored at 25°C/60% RH and 40°C/ 75% RH over 3 months. This loss in amorphous form was paramount for indomethacin when stored at 40°C/ 75% RH. These results indicated the need for storage and packaging precautions for MN of both drugs to prevent solid-state alterations upon storage which could impact on MN mechanical strength and dissolution in the skin. The MNs formed from both drugs, using the melt dissolvable microneedle technology, were found to be physically strong and capable of penetrating ex-vivo pig ear skin. The research presented illustrated that estradiol and indomethacin DMN can be manufactured using a melt DMN technology, but packaging and storage precautions are required to stabilise the drug solid-state form.
Examining fathers’ feeding practices with their children
(University College Cork, 2021-12-21) O'Connor, Simone; Mulcahy, Helen; Leahy-Warren, Patricia
Background: The prevalence of obesity is increasing globally at a rapid rate resulting in a significant threat to public health. Only thirty-seven percent of the Irish population have a normal Body Mass Index (BMI), while 25% of children in Ireland are overweight or obese (Department of Health 2016). Gregory (2015) identified that fathers wish to be more involved in the care of their children than what they currently are. Fathers remain underrepresented in the literature relating to their children’s health outcomes. Aim: The aim of this research is to examine fathers’ feeding practices with their children. Methods: A cross-sectional quantitative research design was utilized. A convenience sample of fathers (n=129) in Ireland who had children 18 years or younger prior to the commencement of the study were recruited through various online platforms. Data were collected using a demographic questionnaire and the Comprehensive Feeding Practices Questionnaire (Musher-Eizenman & Holub 2007). A cross-sectional quantitative research design was utilized. A convenience sample of fathers (n=129) in Ireland who had children 18 years or younger prior to the commencement of the study were recruited through various online platforms. Data were collected using a demographic questionnaire and the Comprehensive Feeding Practices Questionnaire (Musher-Eizenman & Holub 2007). Once data collection was completed the data were coded using the guidelines from Musher-Eizenman & Holub (2007). The response options utilized a 5-point response scale. A Microsoft Excel Sheet was prepared, and data were entered into it. SPSS version 25 was used for analysis. The mean and standard deviation per subscale of the Comprehensive Feeding Practices Questionnaire (Musher-Eizenman & Holub 2007) were calculated, Spearman's rank correlation coefficient (p value) was used to examine the relationship between age of child and each subscale of the Comprehensive Feeding Practices Questionnaire (Musher-Eizenman & Holub 2007) and the Mann–Whitney U test was used to exam the relationship between child gender and each subscale of the Comprehensive Feeding Practices Questionnaire. Results: Of 129 respondents, almost half were in the 35-44 age range, only 5.4% were between the ages of 18-25 years. The majority identified as white and had achieved third level qualifications. Most responses were based on children ages 2 to 10 years old, and forty-five percent answered in relation to male children. Ninety-three percent of respondents were not concerned about their child’s weight, while 89% categorised their child’s weight as ‘average’. The feeding practices used most frequently by respondents were Encourage Balance and Variety (M 4.66(SD 0.5)), Modelling (M 4.3(SD 0.8)) and Monitoring (M 4.01(SD 0.91)). Fathers’ feeding practices were found to be the similar regardless of gender. Conclusion: Fathers have become more involved in the routine tasks of childcare which were once seen as the mother’s role (Taylor et al., 2013). Despite this the Mixed Methods Systematic Review (MMSR) showed that fathers were underrepresented in the literature. The MMSR found that fathers did have concerns regarding their children maintaining a healthy weight. In the current study most respondents were not concerned about their child’s weight. Fathers’ feeding practices were found to be similar regardless of gender, while they varied with child age. The majority of respondents (93.8%) were not concerned about their child’s weight. Fathers’ feeding practices were found to be similar across both genders. Findings of this study should be used to inform healthcare professionals’ interventions with fathers with regard to their feeding practices and ensure that they are included in all parenting interventions. Based on these findings it is recommended that future studies using the Comprehensive Feeding Practices Questionnaire (Musher-Eizenman & Holub 2007) with a larger probability sample would further inform the application of appropriate clinical and parenting interventions. Implications for clinical practice: Healthcare Professionals should provide education to both fathers and mothers involved in relation to their children’s health. If both parents attend their child’s healthcare visits, healthcare professionals should focus advice, information, and questions equally towards both parents.
Exploring the daily life experiences of UCC registered doctoral [PhD/ MD/ Practitioner Doctorate] students and how the UCC “Everyday Matters: Healthy Habits for University Life” digital badge impacted their daily life and well-being
(University College Cork, 2022) Skipp Prendergast, Alison; Hunt, Eithne; Usher, Ruth; Bank of Ireland
Background - Poor mental health and well-being among university students, including doctoral students, is a growing concern globally. Engaging in occupations every day and maintaining occupational balance is believed to improve health and increase well-being. However, little is currently known about the daily life, occupational balance, and well-being of doctoral students. Whole university approaches to promoting student well-being and success are urgently needed, along a continuum of support including universal, targeted, and intensive interventions. The “Everyday Matters: Healthy Habits for University Life” digital badge (EMDB) is an occupation-based time-use and well-being universal intervention offered to doctoral students as a cocurricular micro-credential at University College Cork (UCC). This study explored and described the daily life experiences of doctoral students and how pursuing their degree impacted their occupational balance and well-being, as well as examined doctoral students’ experience of participating in the EMDB. Method - Purposive sampling methods were used in this qualitative interpretive descriptive study to recruit 10 UCC PhD/MD/Practitioner Doctorate students who completed the EMDB. Data were generated through individual semi-structured interviews and thematic analysis was completed. Findings - Doctoral students have a range of roles, responsibilities, and occupations that they need to and want to engage in on a daily basis. For many, balancing their daily occupations and roles alongside their doctoral degree is challenging. Undertaking a doctoral degree can have both a positive and negative impact on well-being. The EMDB successfully supported the daily lives and well-being of doctoral students. Conclusion - Obtaining an insight into the perspectives and experiences of students allows a better understanding of the students’ doctoral journey. Supporting the well-being of doctoral students is essential to enhance their doctoral journey and assist them in successfully completing their degree.
The impact of variation in freezing and thawing process parameters on the critical quality attributes of a monoclonal antibody
(University College Cork, 2019-09-23) Day, Neil; Crean, Abina; Vucen, Sonja
Therapeutic proteins or biopharmaceuticals have been playing an ever-increasing role in the treatment of human diseases over last 40 years. One of the main challenges with manufacture of these proteins is the stabilization of both the finished product and its processing intermediates during storage. Freezing and frozen storage is widely applied to improve stability of the bulk drug substance. The process of freezing a protein results in stresses that can cause protein degradation and subsequent aggregation. The aim of this project was to evaluate the effect of parameters involved with freezing and thawing of a formulated monoclonal antibody solution in polycarbonate bottles and to assess the scalability of these experiments to the respective full-scale commercial process. Initial experiments were performed to characterise the formulation and develop analytical methods that can detect change in unfolding and aggregation of a fully human IgG1 monoclonal antibody (‘Protein Y’). A designed set of experiments were then executed to understand the effect of parameters involved in freezing and thawing steps of a formulated therapeutic protein solution on protein aggregation and perturbations in tertiary structure. Results showed that the processing parameters studied caused significant variation in freeze and thaw process times, with the factors causing slower rates of freeze and thaw also shown to cause changes in the tertiary structure of Protein Y. Despite the observed changes in tertiary structure, the effect on aggregation was less pronounced, with only a significant change noted for the polydispersity index (PdI), as measured by dynamic light scattering (DLS).
The influence of gender on paternal involvement in the treatment process of a child or adolescent with an eating disorder
(University College Cork, 2022-06-29) O'Sullivan, Hazel; O'Donovan, Áine; Goodwin, John
Aim: To identify factors that influence paternal engagement in the treatment process of a child or adolescent with an eating disorder. Background: Eating disorders are complex mental health issues and are exacerbated by a high mortality rate. Adolescence is the period of development when an eating disorder typically commences. International and national guidelines recommend the involvement of the family in the treatment process. However, barriers can exist on both an organisational and on an individual level. The family is an important source of support, yet there is a lack of research pertaining to the factors that facilitate or prevent fathers from participating in the treatment process. Method: A scoping review of the literature was undertaken to identify what key information existed within the current literature and research pertaining to the topic under examination. Thirteen studies were identified as pertinent to the research question posed. Following analysis, these studies identified the importance of parental involvement in the treatment process but pointed to fathers assuming a more peripheral role. Thus, to further understand the processes that contributed to paternal engagement this research sought to further examine the paternal role within the treatment process. It was determined that a qualitative descriptive approach would best suit the research aim. Data were obtained by conducting focus groups with a total of seven fathers agreeing to participate in two focus groups. Both focus groups were guided by a semi-structured interview guide. A qualitative content analysis approach was used to analyse the data regarding paternal experiences of engagement in the treatment process. Findings: Four themes were generated from the data. These were; fathers didn’t see this coming, no one place for one person to go alone, we are not as in touch with our children and the eating disorder as a mental illness. Conclusion: Fathers described themselves as on the periphery of the family, they identified themselves as experiencing things differently to mothers with a belief their role was to provide support to their wives and children within the treatment process. Impact: Healthcare providers need to be aware of the contribution of gendered roles within the family system, and the need to consider this when working with families within the treatment process.
An investigation on proteolysis of the ACE2 receptor and its involvement in the cellular uptake and transmission of SARS-CoV-2
(University College Cork, 2021-12-21) Wakerlin, Samantha Leigh; McCarthy, Justin V.; Lindsay, Andrew; Coleman-Vaughan, Caroline
The renin-angiotensin system (RAS) is a key physiologic signalling network in blood and tissue homeostasis in humans. Angiotensin-converting enzyme 2 (ACE2) is a key regulator of the protective axis in RAS signalling as it antagonises the mechanisms of Angiotensin II (Ang II), the major vasoactive peptide of the RAS that can be dysregulated and overactive in disease states. The type I transmembrane protein can also function as a viral receptor, as ACE2 has recently been identified as the host receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 undergoes ectodomain shedding by ADAM17 and other host cell proteases, resulting in the release of its catalytic ectodomain into the extracellular space and the C-terminal fragment (CTF) secured in the membrane. Ectodomain shedding is a prerequisite for further cleavage by gamma-secretase in a two-step mechanism known as regulated intramembrane proteolysis, a common fate of many known receptors that function as viral targets. Given the structural similarity of ACE2 to other known substrates of gamma-secretase, the hypothesised role of ACE2 as a substrate for the protease was explored. Here, we show that the ACE2 CTF product of ADAM17/TMPRSS2 shedding is subsequently cleaved by the gamma-secretase protease to produce an intracellular domain (ICD) that is released within the cell. Pharmacological inhibition of gamma-secretase prevents generation of the ACE2 ICD and leads to the accumulation of membrane-anchored ACE2 CTF lacking the catalytic ectodomain. These observations demonstrate that ACE2 is a substrate for gamma-secretase proteolysis, providing a novel pathway for cellular trafficking of ACE2 that may have therapeutic potential in protective RAS signalling or antiviral immunity.

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